Nanomedicine and Healthcare Systems

The chapter presents an outlook on the recent techniques of developing nanoscale medicines. With advancement in technology, nanoscale therapeutics is slowly becoming the future of medicine and smart diagnostics. The combined activity of therapeutic agents with assistance of nanomaterials have proved effective in troubleshooting the issues concerned with the conventional therapeutic techniques. Despite of these benefits, improvement in certain issues like side effects and toxicity needs to be studied extensively before real-time application in biological systems. Thus, in this chapter, emphasis has been made on understanding the concept of a nanomaterial-based therapeutic system with recent advances and exploration of the characteristics of nanomaterials which would allow us to further develop strategies that are supportive towards effective treatment and disease diagnosis.

Cytochalasin B Treatment and Osmotic Pressure Enhance the Production of Extracellular Vesicles (EVs) with Improved Drug Loading Capacity

Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment.

Dosing Time Matters? Nighttime vs. Daytime Administration of Nifedipine Gastrointestinal Therapeutic System (GITS) or Amlodipine on Non-dipper Hypertension: A Randomized Controlled Trial of NARRAS

Background: Non-dipper hypertension is often characterized by a blunted decrease of nocturnal blood pressure (BP) and is associated with increased risk of target organ damage and cardiovascular (CV) events, while the optimal treatment strategy is yet to be established. This trial was designed to evaluate whether nocturnal BP reduction and arterial stiffness improvement differ from antihypertensive agents and time of administration.Methods: Young and middle-aged adults (18–65 years) with non-dipper hypertension were randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily for 8 weeks, either taken in the morning or at night. Dose was doubled at 4-week if BP is not at goal. Twenty-four hour ambulatory BP monitoring (ABPM) and arterial stiffness were evaluated before and after 8 weeks of pharmacotherapy. The primary efficacy measure was the average nighttime systolic BP reduction.Results: A total of 98 non-dipper hypertensive patients (mean age 46.3 years) were randomized during Dec, 2016 and Dec, 2020, of whom 72 (73%) patients completed all ABPM and follow-up evaluations. Nighttime systolic BP significantly reduced at 8 weeks vs. baseline with nifedipine GITS or amlodipine, irrespective of dosing at nighttime (−9.9 vs −9.9 mmHg, P > 0.05) or daytime (−11.5 vs. −10.9 mmHg, P > 0.05). No difference was seen between these two agents, when combining the data of nighttime and daytime dosing together (−10.8 vs. −10.5 mmHg, respectively, P = 0.898). Daytime, 24-h systolic BP, diastolic BP at different time and pulse wave velocity reduced significantly and comparably, and recovery of dipping rhythm were similar among groups.Conclusion: Nighttime dosing of long-acting antihypertensive preparations, nifedipine GITS or amlodipine demonstrated similar effects on nocturnal BP reduction, dipping rhythm restoration and arterial elasticity improvement in younger subjects with non-dipper hypertension. These effects were comparable with morning dosing.

Comparative analysis of pharmacokinetic parameters of transdermal and intramuscular administration of Galavit®

Introduction. Immunomodulator Galavit® is a promising domestic drug for the prevention and treatment of various infectious diseases. Earlier, the authors have developed and investigated in vitro its new dosage form – transdermal therapeutic system (TTS). Positive results from experiments made it possible to proceed to the study of the pharmacokinetic parameters of Galavit® TTS in animals.Objective: to compare the pharmacokinetic parameters of intramuscular and transdermal administration of immunomodulator Galavit® in animal experiments.Materials and methods. Sodium aminodihydrophthalazinedione was used as a substance in the form of a powder to prepare a solution for intramuscular administration of 100 mg (trade name Galavit®, manufacturer SELVIM LLC). The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 4.5–5.0 kg. Serum sodium aminodihydrophthalazinedione concentrations in animals were determined by highperformance liquid chromatography using a specially developed technique.Results. In contrast to the injection method, a prolonged and uniform inflow of the drug substance (MP) into the body is observed for percutaneous administration of sodium aminodihydrophthalazinedione. The maximum serum Galavit® concentration for a 40 mg dose (0.172 ± 0.054 μg/mL) and for a 80 mg dose (1.16 ± 0.22 μg/mL) remained at a constant level for 9 and 8 hours, respectively. The relative bioavailability of the Galavit® transdermal therapeutic system was 0.65 and 1.06 for the same doses.Conclusion. Application of Galavit® 80 mg transdermal therapeutic system provides bioavailability that is similar to the intramuscular administration of this drug at the same dose. At the same time, its maximum serum concentration significantly decreases and the retention time of Galavit® in the body increases by more than 10 times, which can contribute to prolongation of the drug effect. Due to the current growing interest in the use of immunomodulator Galavit® for coronavirus infection COVID-19, the development and study of a new dosage form is a promising task

Η Θεραπευτική σχέση στη συστημική ψυχοθεραπεία οικογένειας και ζεύγους: απόψεις σε εξέλιξη

The relationship between therapist and client plays a central role in the quality and effectiveness of psychotherapy, independently from the therapeutic approach adopted by the therapist. The therapeutic relationship in the frame of Systemic Family and Couple Psychotherapy (SFCP), presents several peculiarities, especially when displayed in the "classical" therapeutic context of systemic psychotherapy, where complex and multifaceted relationships develop between therapists and family members, in front and through the one-way mirror, forming a network of "multiple bonds". Modern views on therapeutic relationship in SFCP have been influenced by the development of the "second order cybernetic", since the late 1980s, and the subsequent "linguistic shift", according to which the therapist, as a part of the therapeutic system, dialogues with family members, contributing to co-constructs new realities, as a therapeutic change cannot result from a didactic / guiding relationship. In this context, the emotions and feelings of the members of the therapeutic system come to the fore, whilst the issue of clients’ resistance to the treatment process is completely redefined. The research regarding the therapeutic relationship in the systemic approach, using both quantitative and qualitative methods, focused on a variety of dimensions, e.g., the impact of the session context and the used techniques, the degree of empathy between therapists and clients, and the therapeutic alliance that develops between them. In more recent years, the provision of mental health services using digital practices raised new challenges and concerns regarding the development of the therapeutic relationship in the new conditions of cooperation between therapist(s) and client(s) in online settings.

Sequence-Defined Nanotubes Assembled from IR780-Conjugated Peptoids for Chemophototherapy of Malignant Glioma

Near-infrared (NIR) laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy. However, insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen (1O2) distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes. To achieve high tumor killing efficacy, one of the solutions is to employ the combinational treatment of phototherapy with other modalities, especially with chemotherapeutic agents. In this paper, a simple and effective multimodal therapeutic system was designed via combining chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain. IR-780 (IR780) dye-labeled tube-forming peptoids (PepIR) were synthesized and self-assembled into crystalline nanotubes (PepIR nanotubes). These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density; thus, a self-quenching of these IR780 molecules was significantly reduced. Moreover, the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells. Given the unique properties of peptoids and peptoid nanotubes, we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.